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Biomedical subjects

K D Stoll

Publications and source records attributed to K D Stoll.

At least 19 recordsLinked to original sources
PubMed2004

Clinical trials with sigma ligands.

So far, sigma-ligands have been investigated for several indications in human studies in functional diarrhea as a model of somatoform disorder (igmesine), depression (igmesine, opipramol), anxiety (opipramol and--in animal models--siramisine), schizophrenia (panamasine, SL 82.0715, rimcazole, DuP 734, BMY 14 802), and somatoform disorders (opipramol). Results for schizophrenia failed to be clear cut and so investigations have apparently stopped for the time being. The Sigma-1-selective igmesine (200 mg) showed good results in a phase-1-model of functional diarrhea and some promising results in depressed patients. However, further development has been stopped due to marketing reasons, which is also true for siramasine, a selective sigma-2-ligand with anxiolytic properties. Opipramol, which, apart from a sigma-1- and 2-receptor liability, also possesses histamine-H(1)-antagonistic properties in connection with lower affinities for D(2) and 5-HT(2A) showed broad efficacy in generalized anxiety disorder and somatoform disorders. The receptor profile of opipramol and the results of studies of the selective sigma site ligands siramisine and igmesine suggest that opipramol acts pharmacologically and clinically via sigma receptors.

Animals↗
PubMed2001

Opipramol for the treatment of generalized anxiety disorder: a placebo-controlled trial including an alprazolam-treated group.

Opipramol, a drug widely prescribed in Germany, is a tricyclic compound with no reuptake-inhibiting properties. However, it has pronounced D2-, 5-HT2-, and H1-blocking potential and high affinity to sigma receptors (sigma-1 and sigma-2). In early controlled trials, anxiolytic effects were revealed. However, those studies were performed before the concept of generalized anxiety disorder (GAD) was established. Because of the interesting receptor-binding profile and promising results of the early clinical trials, the authors performed a state-of-the-art placebo-controlled trial using alprazolam as an active control. Three hundred seven outpatients with GAD were included. After a 7-day single-blind placebo washout, patients were randomly assigned to receive either opipramol (final dose, 200 mg/day), alprazolam (2 mg/day), or placebo and were treated for 28 days. The efficacy of both active compounds was higher than the effects with placebo treatment. There were statistically significant differences (p < 0.05, according to the analysis of covariance) in the main outcome criterion (baseline-adjusted final means of an intent-to-treat analysis of the total scores on the Hamilton Rating Scale for Anxiety) and in secondary efficacy parameters, with global improvement of 47% for placebo and significantly more for opipramol (63%) and alprazolam (64%). Regarding safety and tolerability, no substantial differences in the number of adverse events observed between treatment groups were obvious. Sedation seemed more pronounced with alprazolam treatment than with opipramol or placebo. In this trial, it was demonstrated for the first time that opipramol, a strong but nonselective sigma site ligand, possesses anxiolytic efficacy superior to placebo in the treatment of GAD.

Adolescent↗
PubMed2000

Opipramol for the treatment of somatoform disorders results from a placebo-controlled trial.

Although somatoform disorders are highly prevalent, so far there is no established pharmacological treatment. Opipramol is a psychopharmacon widely prescribed in Germany. Early trials with opipramol showed the drug's effectiveness in anxiety states coupled with somatic complaints. Therefore, the efficacy of opipramol in somatoform disorders was evaluated using adequate clinical trial methods. A multicentre, randomized, 6-week, placebo-controlled clinical trial was performed in a total of 200 patients suffering from somatoform disorders according to ICD-10. In the main outcome criterion, the somatic subscore of the Hamilton Anxiety Scale, and in nearly all other outcome criteria opipramol (200 mg/day) was statistically more effective than placebo. A similar number of adverse events was noted in both groups. The results of this first-placebo-controlled study in somatoform disorders suggest efficacy of opipramol in this indication but need replication.

Adolescent↗
PubMed1992

Hyponatremic coma under oxcarbazepine therapy.

Oxcarbazepine (OXC) is considered to be a promising new antiepileptic drug with similar efficacy and better tolerability compared to carbamazepine (CBZ). However, hyponatremia is supposed to occur even more often than with CBZ. We report on a patient who developed hyponatremic coma under OXC with a serum sodium level of 115 mmol/l, the second published case of OXC-induced hyponatremia with serious clinical adverse effects.

Anticonvulsants↗
PubMed1989

Efficacy and tolerability of a new antipsychotic compound (savoxepine): results of a pilot-study.

Savoxepine is a new tetracyclic compound displaying potent neurolepticlike effects in pharmacological studies. Of particular interest is its preferential binding to dopamine-2 receptors in the hippocampus, which leads to the hypothesis that savoxepine may exert antipsychotic effects at doses not inducing extrapyramidal side-effects. In an open pilot-study 18 patients suffering from acute schizophrenic psychoses or paranoid syndromes were treated with savoxepine in an individually adapted dose range from 0.50 to 10 mg per day. A good antipsychotic efficacy could be demonstrated in 10 of 16 patients. Savoxepine was found to be generally well tolerated. Contrary to expectations, mild or moderate extrapyramidal side-effects, especially of the parkinsonian type, were registered. Future research has to test the suggested advantage of savoxepine in comparison with other neuroleptic drugs.

Adult↗
PubMed1988

Investigations on the intraindividual constancy of the ratio of carbamazepine to carbamazepine-10,11-epoxide in man.

The constancy of the ratio of carbamazepine (5H-dibenzo[b,f]azepine-5-carboxamide) to carbamazepine-10,11-epoxide was investigated in epileptic patients receiving carbamazepine (Tegretal) monotherapy. We observed a significant interindividual difference, but not between the times in a single patient. Together with the similarly evaluated concordance coefficient, this indicates a certain intraindividual constancy of the ratio between carbamazepine and its epoxide. The carbamazepine:carbamazepine epoxide ratio was dose-dependent, while a sex difference could not be demonstrated.

Adolescent↗
PubMed1985

[Antiepileptic monotherapy and combination therapy of simple focal seizures].

According to present state of literature complete seizure control can be obtained in about 50% of patients with simple partial seizures. In several studies on previously untreated patients with simple partial seizures most patients became seizure-free with carbamazepine or phenobarbital or phenytoin or primidone or valproic acid used as monotherapy. Previous experience has shown that in patients whose seizures are not completely controlled by monotherapy drug combinations like carbamazepine with phenobarbital or primidone or valproic acid and phenytoin with phenobarbital or primidone or valproic acid should be initiated. Several animal experiments are suggestive for a synergistic effect of different antiepileptic drugs. In a previously published study on carbamazepine monotherapy, 6 out of 9 patients with simple partial seizures became seizure-free or improved markedly by this treatment.

Adolescent↗
PubMed1984

[Combination therapy with carbamazepine and valproic acid in problem cases at an outpatient epilepsy clinic].

A total of 64 problem patients with epilepsy (42 retrospective evaluations, 22 prospective cases) was treated with the combination of carbamazepine and valproic acid. Most frequent seizure types were tonic clonic (focal origin or primarily generalized), complex partial ones, and absences. Best results were observed in patients with tonic clonic seizures in contrast to complex partial ones. The pattern of adverse reactions (none of significant severity) was according to those of monotherapies with the compounds. In cases with relevant improvement serum levels of carbamazepine and valproic acid were within the range commonly described for monotherapies.

Adult↗
PubMed1978

[Clinical trial of mepiprazol in the treatment of neurotic inpatients (author's transl)].

Within a controlled double-blind clinical trial the psychopharmacological effect of mepiprazole was tested against placebo in the treatment of neurotic inpatients. Some results of the recorded psychophysiological parameters (tremor, reaction time and flicker fusion threshold) as well as the scores on a symptom checklist for neurotic patients (post hoc divided into three scales by means of factor analysis: anxiety, depression and weaping) indicate a tranquilizing effect of mepiprazol. These findings are discussed critically with regard of methodological problems of testing tranquilizers in psychiatric hospitals.

Adolescent↗
PubMed1977

Effect of pyritinol-GCl on blood flow and oxidative metabolism of the brain in patients with dementia.

In order to test whether and in what way pyritinon-HCl affects cerebral blood flow and oxidative metabolism in patients with organic brain disorders, the following parameters were measured in a group of 87 patients: cerebral blood flow using the Kety and Schmidt method, cerebral consumption of oxygen and glucose, and also CO2 and lactate ouptut. 45 out of the 87 patients were given pyritinol in a dose of 900 or 1000 mg/day, 42 out of 87 patients formed a control group and were given 500 mgof 5% laevulose i.v. daily for the average duration of the study of approximately 3 weeks. The results can be summarised as follows: 1. Cerebral blood flow and oxidative metabolism are changed in patients with organic brain disorders in different ways voth as regards quality and quanitity. Findings from earlier investigations could thus be confirmed. 2. When laevulose only was used, the parameters measured did not alter on average. In addition to deteriorations in the findings, spontaneous improvements or normalisationof previously disturbed cerebral blood flow and cerebral metabolism values were also abserved. 3. Pyritinol-HCl usually improved previously disturbed cerebral glucose metabolism significantly. An effect on disturbed cerebral blood flow or pathologically changed cerebral oxygen consumption was not found.

Adult↗
PubMed1976

[Double-blind study on the therapy of postural hypotension in psychotic patients under psychotropic medication (author's transl)].

13 psychotic patients developing various degrees of postural hypotension during neuroleptic or antidepressant treatment were additionally given either placebo or a mineralocorticoid or a sympathomimetic drug. As shown by Schellong tests during therapy the best effect on postural hypotension was achieved by the mineralocorticoid. The statistical evaluation of the randomised study was significant.

Adult↗